Download 1. Medical Condition ATTENTION DEFICIT HYPERACTIVITY

Medical Information to Support the Decisions of TUE Committees
Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
1. Medical Condition
ATTENTION DEFICIT HYPERACTIVITY DISORDER
(ADHD) IN CHILDREN AND ADULTS
Introduction
Attention-deficit/hyperactivity disorder (ADHD) is one of the most
common neurobehavioral disorders. ADHD is a chronic disease which
begins in childhood (estimated prevalence rates vary from 3% to 9.9%),
the symptoms of which can persist through adolescence into adulthood
and become lifelong.1-3 This has been confirmed in long-term follow-up
studies which have demonstrated the persistence of symptoms in many
adults diagnosed with ADHD in childhood.4–8 A meta-analysis of follow-up
ADHD studies reported that 15% of all cases show persistence of
symptoms beyond childhood, and 40%–50% of patients continue to have
a partial diagnostic status and impairment in their adult life.9-10
ADHD is characterized by symptoms of inattention and/or hyperactivityimpulsivity that interfere with functioning or development and are present
in more than one setting. ADHD may cause difficulties at school, in the
work place, and in the social environment. Children with ADHD may
experience significant adaptation problems because their functional level
and behavior may not correspond to their chronological age or expected
development level.11
ADHD sufferers have a high incidence of co-morbidities. A recent study
showed the most frequent co-morbidities in children to be learning
disorders (47.3%), conduct disorders (28.6%), and oppositional defiant
disorder (22.1%).12,13
Other relevant studies have reported co-morbid depressive disorder rates
of 5%–47% in children and adolescents with ADHD.14-16. Evidence from a
meta-analysis of prospective studies in children with ADHD suggests that
children with ADHD also have a higher risk of developing substance use
disorders and cigarette smoking than those without ADHD.17
These co-morbidities are also present in the adult population with ADHD.
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Medical Information to Support the Decisions of TUE Committees
Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
2. Diagnosis
A. Medical History
The diagnosis of ADHD is a clinical one and requires a complete
medical evaluation to detect specific symptoms that have to be
present in consistent contexts and with a persistent level of
deterioration.19
The presence of symptoms is directly obtained from the patient (child
or adult), parents and other family members or spouses, teachers and
work colleagues. Multiple scales have been created to identify specific
symptoms in order to diagnose ADHD, but the most commonly used
diagnostic criteria are those of the DSM-V (Diagnostic and Statistical
Manual of Mental Disorders Fifth Edition May 2013).20
The essential feature of attention deficit/hyperactivity disorder is a
persistent pattern of inattention and or hyperactivity-impulsivity that
interferes with functioning and development. The requirement that
several symptoms be present before age 12 years conveys the
importance of a substantial clinical presentation during childhood.
Manifestations of the disorder must be present in more than one
setting (e.g. home, school, work). There is an exclusion that the
symptoms should not occur exclusively during the course of
schizophrenia or another psychotic disorder and are not better
explained by another mental disorder (e.g. mood disorder, anxiety
disorder, dissociative disorder, personality disorder, substance
intoxication or withdrawal)20
In most parts of the world, clinicians involved in the diagnosis and
treatment of ADHD include pediatricians, psychiatrists and clinical
psychologists.
B. Diagnostic criteria
1) Evaluation by a pediatrician, psychiatrist or other physician who
specializes in the treatment of ADHD/ADD;
2) Clinical history and examination findings supporting the diagnosis
that must meet the DSM-V criteria. (Children must have at least
6 symptoms from either or both the inattentive and hyperactivity
sections. Older adolescents and adults (over the age 17 years)
must present with 5 symptoms and several of these symptoms
should have been present prior to the age of 12 years.20)
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Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
3) There should be evidence of the use of a comprehensive validated
diagnostic scale assessing symptoms and impairment. These could
include but are not limited to:
a) Adults:
ACDS, CAADID, Barley, DIVA
b) Children: Vanderbilt, K-SADs, DISC, Connors21, SNAP
4) Reports from non-medical personnel, which can include teachers,
parents or colleagues, reporting on behavior and symptom impact in
realms of life other than sport (i.e. home, school, work) can assist in
demonstrating that the impairments occur in multiple settings.
5) When ADHD is diagnosed for the first time as an adult (>18 years), a
second opinion from an independent specialist medical practitioner
(usually psychiatrist) confirming the diagnosis, may be required
unless the presence of symptoms in childhood can be confirmed by
other reliable independent sources (i.e. psychologists reports, school
reports etc.).
6) In athletes > age 18 the medical evaluation should particularly
consider medical and mental health co-morbidities (e.g. depression)
and history of brain injuries, particularly in contact sports.
7) Description of the use of behavioral therapy and other forms of nonmedication treatments is helpful.
3. Medical best practice treatment
A. Name of prohibited substance
Sympathomimetic
psychostimulants
(methylphenidate
and
amphetamine derivatives) form the basis of the treatment of ADHD in
most countries around the world. Pharmacologic treatment with
stimulants usually has the direct effect of reducing activity and
increasing attention, with the effects being evident within a short
period of time.22 It should be noted that the choice of first line
pharmacological treatment in ADHD varies across countries and
Atomoxetine (Strattera) is a non-prohibited substance that is also
used in the treatment of ADHD and is considered first line in some
countries.
B. Route
Oral
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Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
C. Dosage and Frequency
Both methylphenidate and amphetamine compounds come in
immediate release (active for 2-5 hours) and extended release (6-14
hours) preparations. There are also combinations of immediate and
extended release formulations in single tablets. Combinations of these
preparations are often used to achieve the best symptom control.
Maximal dosages based on body weight are too variable across the
world to use as guidelines in this document. Optimal doses are best
decided on an individual basis whilst adequately monitoring for
symptom control and side effects.
It should be noted that there is no necessity to cease treatment
during competition periods. It is now generally considered that
cessation of treatment can have a number of negative effects
including an adverse effect on symptom control, which can take time
to re-establish. This destabilizing of symptom control can also lead
athletes to have an increase in risk taking behaviors and can increase
their involvement in conflict situations (e.g. altercations with
referees).
Patients usually find that their symptoms are best controlled on a
regular, stable dose of stimulant medication once their optimal dosing
regimen has been achieved. For this reason intermittent use,
including PRN dosing is not generally recommended.
In newly diagnosed ADHD patients there will be dosage changes until
optimal management is achieved. Given this, a range of dose may be
appropriate on the approval certificate with a maximal 12 months
approval. Allowing for the next approval to be granted for a stable
dose. This prevents the need for repeat TUE applications in the first
year for changes of doses whilst stabilizing the symptoms.
Any change of medication or significant adjustment of the dosage
should result in a re-submission or advisement to the ADO granting
the TUE.
Side effects of stimulants for consideration by treating doctors
Some of the more common side effects reported with the use of
psychostimulants include insomnia, reduced appetite, headaches and
jitteriness, but these are usually tolerable.24 There is evidence that
stimulants can increase the blood pressure and heart rate with
relative contra-indications to use in those with hypertension,
arrhythmias and cardiomyopathies.
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Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
There are some studies linking increased cardiac events with the use
of stimulants. The studies in the younger population indicate that
there is no significant risk in an otherwise healthy population. The
studies in adults are more varied but there remains insufficient
evidence to advise against the use of stimulants for the treatment of
ADHD in an otherwise well young adult. Despite this it would be
advisable to complete a thorough cardiovascular history and
examination in all patients who are being prescribed stimulants. There
are no current recommendations for mandatory pre-screening
(specifically ECGs) based solely on concerns of the risk of
psychostimulants. Literature reviews have confirmed that the risk of
developing long-term substance abuse whilst taking psychostimulants
for the treatment of attention deficit hyperactivity disorder (without
co-morbidities) is small and may even decrease with proper
treatment.26
There is no evidence that the therapeutic use of stimulants in the
treatment of ADHD increases aggressive behavior. There are however
reviews suggesting that untreated ADHD patients are more likely to
become involved in risk taking behavior and conflict situations. Some
treatment review articles indicate lack of control of aggressive
behavior can be an indication to increase the dose of psychostimulant
medication.
C. Recommended duration of treatment
The pharmacological treatment of ADHD is usually long term over
many years.
It is highly recommended for any athlete on continued therapy with
methylphenidate or dextroamphetamine to undergo an annual review
by a specialist in the management of ADHD.
4. Other non-prohibited alternative treatments
Atomoxetine (Straterra) has been identified as a non-prohibited alternate
treatment for some patients with ADHD. This medication is considered by
many to be less effective than stimulant medication and it has a different
side effect profile which includes somnolence, sexual side effects and
occasionally liver complications. In addition, this medication is not
available in all countries. At this point, Atomoxetine is considered a
second line treatment for ADHD in most countries because of its lower
efficacy and side effect profile.
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Medical Information to Support the Decisions of TUE Committees
Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
As it is generally considered a second line treatment, it is not necessary
to demonstrate a failed trial of Atomoxetine prior to the acceptance of
methylphenidate or amphetamine for a TUE.
Otherwise, apart from some behavior-modifying techniques, treatments
with non-prohibited substances have not been shown to be effective.
5. Consequences to health if treatment is withheld
Untreated, ADHD is widely recognized as having detrimental effects on
the quality of life and psycho-social development of the patient. Comorbid psychiatric conditions may manifest if ADHD is left untreated.
6. Treatment monitoring
Following the initiation of treatment, monitoring should be undertaken to
assess the effectiveness of treatment until stabilization has been
achieved. This may require 2-3 monthly reviews. Symptom scales can be
helpful in these reviews. Once stabilized on a dosage regimen, regular
review appointments are recommended and the maximum time between
specialist reviews should be 12 months.
7. TUE validity and recommended review process
Due to the chronic nature of ADHD, a TUE, in the case of a welldocumented, long standing diagnosis of ADHD can be granted for up to
four (4) years at a time.
An initial application for a newly diagnosed ADHD patient may be more
appropriately approved for 12 months until a stable dose is achieved.
Evidence of yearly reviews by the treating clinician must accompany a
TUE reapplication.
8. References
1) International Consensus Statement on ADHD. Clin Child Fam Psychol
Rev. 2002; 5:89–111.
2) Kutcher S, Aman M, Brooks SJ, et al. International consensus
statement on attention deficit hyperactivity disorder (ADHD) and
disruptive behaviour disorders (DBDs): clinical implications and
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Medical Information to Support the Decisions of TUE Committees
Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
treatment
practice
2004;14:11–28.
suggestions.
Eur
Neuropsychopharmacol.
3) Wilens TE, Faraone SV, Biederman J. Attention-deficit/hyperactivity
disorder in adults. JAMA. 2004;292:619–623.
4) Biederman J, Mick E, Faraone SV. Age-dependent decline of
symptoms of attention deficit hyperactivity disorder: impact of remission
definition and symptom type. Am J Psychiatry. 2000;157:816–818.
5) Weiss G, Hechtman L, Milroy T, Perlman T. Psychiatric status of
hyperactives as adults: a controlled prospective 15-year follow-up of 63
hyperactive children. J Am Acad Child Adolesc Psychiatry. 1985;24:211–
220.
6) Barkley RA, Fischer M, Smallish L, Fletcher K. Young adult follow-up
of hyperactive children: antisocial activities and drug use. J Child
Psychol Psychiatry. 2004;45:195–211.
7) Biederman J, Faraone SV, Spencer TJ, Mick E, Monuteaux MC, Aleardi
M. Functional impairments in adults with self-reports of diagnosed
ADHD: A controlled study of 1001 adults in the community. J Clin
Psychiatry. 2006;67:524–540.
8) Mannuzza S, Klein RG, Bonagura N, Malloy P, Giampino TL, Addalli
KA. Hyperactive boys almost grown up. V. Replication of psychiatric
status. Arch Gen Psychiatry. 1991;48:77–83.
9) Boomsma DI, Saviouk V, Hottenga JJ, et al. Genetic epidemiology of
attention deficit hyperactivity disorder (ADHD index) in adults. PloS One.
2010;5:e10621.
10) Faraone SV, Biederman J, Mick E. The age-dependent decline of
attention deficit hyperactivity disorder: a meta-analysis of follow-up
studies. Psychol Med. 2006;36:159–165.
11) American Academy of Pediatrics Clinical practice guideline: diagnosis
and evaluation of the child with attention-deficit/hyperactivity disorder.
Pediatrics. 2000;105:1158–1170.
12) Practice Parameter for the Assessment and Treatment of Children
and Adolescents With Attention-Deficit/ Hyperactivity DisorderJ. AM.
ACAD. CHILD ADOLESC. PSYCHIATRY, 46:7, JULY 2007.
13) Larson K, Russ SA, Kahn RS, Halfon N. Patterns of comorbidity,
functioning, and service use for US children with ADHD, 2007.
Pediatrics. 2001;127:462–470.
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Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
14) Pliszka SR. Comorbidity of attention-deficit/hyperactivity disorder
with psychiatric disorder: an overview. J Clin Psychiatry. 1998;59 (Suppl
7):50–58.
15) Spencer T, Biederman J, Wilens T, Greene R. Principals and Practice.
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Press;
2003.
Pediatric
Psychopharmacology.
16) Wilens TE, Biederman J, Brown S, et al. Psychiatric comorbidity and
functioning in clinically referred preschool children and school age
youths with ADHD. J Am Acad Child Adolesc Psychiatry. 2002;41:262–
268.
17) Wilens TE, Martelon MK, Joshi G, et al. Does ADHD predict
substance-use disorders? A 10-year follow-up study of young adults with
ADHD. J Am Acad Child Adolesc Psychiatry. 2011;50:543–553.
18) Wilens TE, Biederman J, Brown S, et al. Psychiatric comorbidity and
functioning in clinically referred preschool children an school age youths
with ADHD. J Am Acad Child Adolesc Psychiatry. 2002;41:262–268.
19) Valdizán JR, Izaguerri-Gracia AC. ADHD in adults. Rev Neurol.
2009;48(Suppl 2):S95–S99.
20) American Psychiatric Association The Diagnostic and Statistical
Manual of Mental Disorders, Fifith Edition, Washington, DC: American
Psychiatric Association; 2013.
21) Journal of the American Academy of Child & Adolescent Psychiatry.
42(2):193-200, February 2003.
22) Faraone SV, Spencer T, Aleardi M, Pagano C, Biederman J. Metaanalysis of the efficacy of methylphenidate for treating adult attentiondeficit/hyperactivity disorder. J Clin Psychopharmacol. 2004;24:24–29.
23) Conners CK, March JS, Frances A, Wells KC, Ross R. The expert
consensus guideline series: treatment of attention-deficit/hyperactivity
disorder. J Atten Disord. 2001;4(Suppl 1):7–128.
24) Wigal T, Greenhill L, Chuang S, et al. Safety and tolerability of
methylphenidate in preschool children with ADHD. J Am Acad Child
Adolesc Psychiatry. 2006;45:1294–1303.
25) Lerner M, Wigal T. Long-term safety of stimulant medications used
to treat children with ADHD. Pediatr Ann. 2008;37:37–45.
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Medical Information to Support the Decisions of TUE Committees
Attention Deficit Hyperactivity Disorder (ADHD) In Children And Adults
26) Merkel RL, Kuchibhatla A. Safety of stimulant treatment in attention
deficit hyperactivity disorder: Part I. Expert Opin Drug Saf. 2009;8:655–
668.
27) Turgay, A. Aggression and disruptive behaviour disorders in children
and adolescents. Expert Rev Neurother. 2004 Jul;4(4):623-32.
28) Polanczyk G, Silva de Lima M, Lessa B, Biederman J, Rohde A. The
worldwide prevalence of ADHD: a systematic review and metaregression analysis. Am J Psychiatry. 2007; 164:942–948.
29) Kooij et al. European consensus statement on diagnosis and
treatment of adult ADHD. The European network Adult ADHD. BMC
Psychiatry. 2010; 10:67.
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